title: Neisseria meningitidis is structured in clades associated with restriction modification systems that modulate homologous recombination.
abstract: Molecular data on a limited number of chromosomal loci have shown that the population of Neisseria meningitidis (Nm), a deadly human pathogen, is structured in distinct lineages. Given that the Nm population undergoes substantial recombination, the mechanisms resulting in the evolution of these lineages, their persistence in time, and the implications for the pathogenicity of the bacterium are not yet completely understood. Based on whole-genome sequencing, we show that Nm is structured in phylogenetic clades. Through acquisition of specific genes and through insertions and rearrangements, each clade has acquired and remodeled specific genomic tracts, with the potential to impact on the commensal and virulence behavior of Nm. Despite this clear evidence of a structured population, we confirm high rates of detectable recombination throughout the whole Nm chromosome. However, gene conversion events were found to be longer within clades than between clades, suggesting a DNA cleavage mechanism associated with the phylogeny of the species. We identify 22 restriction modification systems, probably acquired by horizontal gene transfer from outside of the species/genus, whose distribution in the different strains coincides with the phylogenetic clade structure. We provide evidence that these clade-associated restriction modification systems generate a differential barrier to DNA exchange consistent with the observed population structure. These findings have general implications for the emergence of lineage structure and virulence in recombining bacterial populations, and they could provide an evolutionary framework for the population biology of a number of other bacterial species that show contradictory population structure and dynamics.
authors.affiliation: Research Center, Novartis Vaccines and Diagnostics, 53100 Siena, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Budroni
authors.forename: Emilio
authors.initials: E
authors.lastname: Siena
authors.forename: Julie C
authors.initials: JC
authors.lastname: Dunning Hotopp
authors.forename: Kate L
authors.initials: KL
authors.lastname: Seib
authors.forename: Davide
authors.initials: D
authors.lastname: Serruto
authors.forename: Chiara
authors.initials: C
authors.lastname: Nofroni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Comanducci
authors.forename: David R
authors.initials: DR
authors.lastname: Riley
authors.forename: Sean C
authors.initials: SC
authors.lastname: Daugherty
authors.forename: Samuel V
authors.initials: SV
authors.lastname: Angiuoli
authors.forename: Antonello
authors.initials: A
authors.lastname: Covacci
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Pizza
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.forename: Duccio
authors.initials: D
authors.lastname: Medini
mesh_terms: D001483:Base Sequence; D007446:Chromosome Inversion / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D015280:DNA Restriction-Modification Enzymes / Q000235:genetics*; D004269:DNA, Bacterial / Q000235:genetics; D005785:Gene Conversion / Q000235:genetics; D005798:Genes, Bacterial / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D016254:Mutagenesis, Insertional / Q000235:genetics; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D009876:Operon / Q000235:genetics; D010802:Phylogeny; D011995:Recombination, Genetic; D013045:Species Specificity
chemical_list: D015280:DNA Restriction-Modification Enzymes; D004269:DNA, Bacterial